Infection by West Nile Virus can lead to encephalitis, or harmful inflammation of the brain. The immune system is critical for controlling viral replication and spread early in West Nile Virus infection, but persistent immune activation causes encephalitis that can result in brain damage even after the virus has been cleared. Recent pharmacologic advances have produced drugs that modulate the body’s immune response and can control inflammation, but these drugs have not yet been tested in conditions of viral encephalitis. In order for patients to benefit from these therapies, clinicians need tools that help identify when excessive immune activity is causing encephalitis.
The key innovation of this project is the combination of noninvasive imaging with novel immune modulating drugs to improve the diagnosis and treatment of encephalitis. Our central hypothesis is that specialized immune cells known as macrophages are key drivers of encephalitis in West Nile Virus infection, and that preventing their activation will preserve memory and other cognitive functions. Our studies will explore and develop noninvasive positron emission tomography (PET) imaging as a tool for diagnosing brain inflammation. We will test our hypothesis utilizing West Nile Virus infection of mice, which captures the key elements of human disease including encephalitis. This model allows us to evaluate existing diagnostic and therapeutic tools currently used in humans for other purposes, from which we will define new clinical applications. We will thus be poised to translate our findings to human studies defining and treating viral encephalitis.
After COVID infection, 10-50% of people experience persistent symptoms such as fatigue, palpitations, insomnia, cognitive problems, and headache – often with significant associated distress and functional impairment. The exact combination of symptoms varies from person to person, and it is expected that the specific causes vary from person to person as well.
Because of this variability, the current recommendation is for an evaluation by a multidisciplinary team. This creates a demand on our medical system that far outstrips current resources, and risks exposing patients to long, complex medical evaluations whose results are hard to interpret. In addition, clinical treatment trials that mix patients with similar symptoms but different underlying causes have high failure rates.
To address these challenges, a team of investigators including Rebecca Hendrickson, MD, PhD (Department of Psychiatry and Behavioral Sciences), John Oakley, MD, PhD (Department of Neurology), and Aaron Bunnell, MD (Department of Rehabilitation Medicine) are testing an online platform to identify patients whose pattern of symptoms suggest a particular underlying cause that is common after certain physiologic (i.e. illness or injury) and psychological stressors: increased adrenergic (adrenaline/noradrenaline) signaling in the brain and peripheral nervous system. We will pair this with a smaller number of detailed in-person assessments to validate our symptom-based measures and characterize associated biomarkers.
Our results will provide a detailed assessment of the patterns of symptoms caused by high amounts of adrenergic signaling that are seen in persistent post-COVID syndrome, how they change over time, and their association with objective measures of cognition and physiology. The project will provide the information needed to begin clinical treatment trials using existing, well-tolerated treatments that modulate adrenergic signaling. We hope the results will also have strong relevance to other potentially related disorders such as Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia.
The objective of this proposal was to investigate the effects of a highly communicable infectious disease leading to severe pneumonia and death (COVID-19) in pregnant women in Washington State. Pregnant women are typically a highly vulnerable group to pathogenic respiratory viruses and have the highest WHO priority for influenza vaccination in a pandemic.
The team’s central hypothesis was that COVID-19 infections in pregnancy increase the risk for spontaneous abortion, preterm birth, stillbirth, intrauterine growth restriction and mental health disorders in the mother. They conducted a multi-site prospective chart review of prenatal and neonatal medical records across the majority of health systems in Western Washington (6 hospitals/hospital systems, >20 investigators). Overall, the Washington State COVID-19 in Pregnancy Collaborative sites captured approximately 61% of deliveries in Washington State during the study period.
The team successfully collected data to establish a large, population-based registry in Washington State. Analyses have been completed of the sociodemographic and clinical outcomes of 240 pregnant patients who contracted COVID-19. Work remains ongoing to calculate infection rates, disease severity, co-morbidity, symptom length and possible vascular injury that could impair fetal growth.
The team will continue working toward research to determine how COVID-19 impacts maternal-child physical and mental health. Further grants have been applied and awarded from the Center of Disease Control, Royalty Research Fund and partnerships with Washington State Department of Health.
Adaptation of evidence-based practices and programs (EBPs) is a necessary component of the implementation process. EBPs must be adapted to function with the constraints of real-world practice settings, providers’ expertise, and patients’ needs. The science of intervention adaptation is hungry for well-defined methods of EBP adaptation to guide decision making. A how-to guide for EBP adaptation titled MODIFI: Making Optimal Decisions for Intervention Flexibility during Implementation, is under development with NIMH funding (F32 MH116623). MODIFI will be disseminated via multiple strategies locally, nationally, and internationally. Dissemination of MODIFI will improve the practice of intervention adaptation by providing practitioners with a how-to guide that is (a) evidence-based, (b) usable, and (c) supported by the expert consensus of implementation practitioners and researchers.
The overall goal of this project is to develop a cell phone app that provides continuous assessment of Warfighter health readiness in real time. We are a subcontractor to Warfighter Analytics using Smart Phones for Health (WASH) program and Charles Rivers Analytics for the subject recruitment portion of the overall project.
The UW objective is to recruit 25,000 participants from across the United States to test a newly designed cell phone app named Health & Injury Prediction and Prevention Over Complex Reasoning and Analytic Techniques Integrated on a Cell Phone App (HIPPOCRATIC App) which gathers real-time data measuring an individual’s latent or developing health disorders with a focus on infectious disease and traumatic brain injury. The app is being developed to more effectively assess Warfighter combat/mission readiness and faster, more targeted healthcare delivery for both civilians and Warfighters.
